High CTNND1, EMP1, or IFITM3 expression predicts poor event-free survival. (A) Event-free survival analysis of US cohort (left) and DCOG/COALL cohort (right) B-ALL patients separated by IKZF1 mutation status as indicated. Log-rank p-values are shown. (B–D) EFS analysis as described for A, but separating cohorts based on median expression of (B) CTNND1, (C) EMP1, and (D) IFITM3. Expression of each gene across samples (determined by RNA-seq for US cohort and microarray for DCOG/COALL cohort with probeset indicated) are shown in Figs. S3 and S4. (E and F) EFS for DCOG/COALL patients grouped by IKZF1 deletion status (E) or BCR-ABL1+/like subgroup status (F), and then further separated based on median expression of CTNND1. (G and H) EFS for DCOG/COALL patients grouped by IKZF1 deletion status, and then further separated based on median expression of EMP1 (G) or IFITM3 (H).

Regulation of IKAROS-repressed genes in mouse and human B-ALL. (A–C) RNA-seq expression (RPKM) of (A) Emp1/EMP1, (B) Ifitm3/IFITM3, and (C) Ctnnd1/CTNND1 in control and Ikaros-kd murine B-ALL with Dox treatments indicated (left), and the in US B-ALL cohort stratified by IKZF1 mutation status (right). P-values from moderated Student’s t test. (D) Western blots of Ctnnd1 and Ikaros protein expression in multiple independent primary control and Ikaros-kd leukemias. Ikaros-kd samples B038, B027, and B031, and control samples B002 and B005 are transgenic leukemias (Fig. 1 and 2 and S1), whereas RV#1044 and #1040 were generated using the retroviral approach (Fig. S2). Actin is a loading control.